The Palliative Care Approach to Nausea & Vomiting

Transcription

1 The Palliative Care Approach to Nausea & Vomiting PCQN September 2016 Conference Call Kana Y. McKee, MD Assistant Professor of Clinical Medicine Palliative Care Program, Department of Medicine University of California, San Francisco

2 Symptoms: General Approach Can result from disease or its treatment Evaluation based on goals of care Base treatment on underlying mechanism if possible or to relief of symptom

3 Nausea and Vomiting Nausea Unpleasant sensation of need to vomit Pallor, sweats, tachycardia, diarrhea Common sx in patients with serious illness: 40% of patients at EOL 70% of patients with advanced cancer One of the most uncomfortable symptoms!

4 The Triggers of Nausea & Vomiting 1 st line of defense: Our Senses 2 nd line of defense: Gut Chemo- and Mechanoreceptors 3 rd line of defense: Receptors in the brain 4 th line of defense: Memory, Learned Behavior

5 Krakauer E. NEJM 2005;352:

6 Mechanisms of Nausea and Vomiting Higher cortical structures Chemoreceptor trigger zone (4th ventricle) D2, NK1, (5HT3) Vestibular system Achm, H1 Vomiting Center: (Medulla) Achm, H1, (5HT3) N/V Mechanical stretch, GI irritation 5HT3 in GI tract, mechanoreceptors, vagal, splanchnic and glossopharyngeal nerves

7 Ms. A Ms. A is a 43 year-old woman with metastatic breast cancer. Her disease has progressed rapidly despite aggressive therapy. She recently developed right arm weakness and was found to have brain metastases in addition to bone, liver, and lung metastases. Ms. A presents to clinic today complaining of 2 weeks of nausea and vomiting.

8 Ms. A Medications: pamidronate, phenytoin, oxycodone prn, ibuprofen, omeprazole, and docusate. Exam notable for tachycardia, dry mucosa, normal abdominal exam, and old right arm weakness. Rectal exam: no stool

9 Questions What are the potential causes of Ms. A s nausea and vomiting? Is there any other workup you would like to perform? How would you approach a treatment plan?

10 History Onset, frequency, and severity of nausea Careful medication review Underlying medical illnesses If cancer: type, location, recent treatments (chemo/xrt/surgery?) Associated sxs Gastritis, reflux, constipation?

11 History: Look for Patterns Early satiety, bloating, relief of nausea w/ small-volume emesis à Gastric stasis Colicky abdominal pain, large-volume bilious emesis à Gastric obstruction Nausea with certain smells or the sight of food à Activation of chemoreceptor trigger zone Motion-induced nausea, vertigo à Vestibular Early morning nausea, headaches, impaired cognition à Increased ICP Anxiety or emotionally induced nausea à Cortical

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13 Evaluation Oral inspection Abdominal exam Rectal exam (r/o impaction) Labs: lytes, BUN, Cr, LFTs, Ca ++, drug levels Imaging KUB or CT abd/pelvis CT brain

14 Ms. A: Differential Diagnosis Medications pamidronate, oxycodone, ibuprofen, phenytoin Metastases brain, liver, peritoneum Constipation Metabolic hyponatremia, uremia, hypercalcemia, liver failure

15 Nausea/Vomiting Treatment: 2 Approaches 1. Mechanism-based Determine likely etiology and target first medication to the cause 80-90% effective in the palliative care population Elegant Assesses all causes systematically 2. Empiric Typically multiple etiologies Start with a 5HT3 antagonist (ondansetron) or dopamine antagonist (eg haloperidol) regardless of underlying etiology Wood et al. JAMA 2007;298: Davis and Hallerberg J Pain Sym Man 2010;39:756-67

16 Mechanism-Based Approach to Initial Management of N/V 1. Thorough evaluation to narrow DDx 2. Determine underlying pathway and neuroreceptor 3. Choose antiemetic targeted against neuroreceptor 4. Initiate antiemetic around-the-clock 5. Titrate antiemetic to max recommended dose if nausea persists 6. Add additional antiemetic aimed at different neurotransmitter if nausea persists 7. Evaluate for additional reversible mechanisms & treat

17 Mechanisms of Nausea and Vomiting Higher cortical structures Chemoreceptor trigger zone (4th ventricle) D2, (5HT3), NK1 Vestibular system Achm, H1 Vomiting Center: (Medulla) Achm, H1, (5HT3) N/V Mechanical stretch, GI irritation 5HT3 in GI tract, mechanoreceptors, vagal, splanchnic and glossopharyngeal nerves

18 Chemoreceptor Trigger Zone Most common cause of N/V near end of life Mediators Dopamine (D2), serotonin (5HT3), NK1 Etiologies Drugs: opioids, digoxin, antibiotics, NSAIDS Metabolic: hypercalcemia, hyponatremia, uremia, hepatic failure Bacterial toxins

19 Chemoreceptor Trigger Zone Treatment Relieve underlying etiology D/C meds, lower dose, PPI if can t stop NSAID Correct electrolytes Treatment: Ondansetron (5HT3) Haloperidol (potent D2 antagonist at CTZ) Prochlorperazine (D2, H1, Achm, 5HT3) Olanzapine (multiple Ds and 5HTs, Achm)

20 Ms. A: Differential Diagnosis Medications pamidronate, oxycodone, ibuprofen, phenytoin Metastases brain, liver, peritoneum Constipation Metabolic hyponatremia, uremia, hypercalcemia, liver failure

21 Mechanisms of Nausea and Vomiting Higher cortical structures Chemoreceptor trigger zone (4th ventricle) D2, (5HT3), NK1 Vestibular system Achm, H1 Vomiting Center: (Medulla) Achm, H1, (5HT3) N/V Mechanical stretch, GI irritation 5HT3 in GI tract, mechanoreceptors, vagal, splanchnic and glossopharyngeal nerves

22 Mechanical Stretch, GI Irritation Mediators 5HT3 in GI tract, GI mechanoreceptors, Vagus nerve (AchM, histamine) Etiologies Mucosal irritation (e.g. candidiasis, XRT) External irritation (e.g. peritoneal carcinomatosis) GI stretch (e.g. constipation, obstruction) Viscus enlargement (e.g. liver, kidney) Dysmotility (gastric, bowel infiltration, opioids, anticholinergics)

23 Mechanical Stretch, GI Irritation: Treatment Relieve underlying cause Treat constipation, gastroparesis Antibiotics for candidiasis PPI for gastritis Ondansetron (5HT3) Note: avoid if patient constipated Promethazine (Anticholinergic/antimuscarinic) Metoclopramide (for gastroparesis, partial bowel obstruction) Olanzapine (multiple Ds and 5HTs, Achm)

24 Mechanisms of Nausea and Vomiting Higher cortical structures Chemoreceptor trigger zone (4th ventricle) D2, 5HT3, NK1 Vestibular system Achm, H1 Vomiting Center: (Medulla) Achm, H1, 5HT2 N/V Mechanical stretch, GI irritation 5HT3 in GI tract, mechanoreceptors, vagal, splanchnic and glossopharyngeal nerves

25 Higher cortical structures Direct stimulation of vomiting center Etiologies: Tumor, mets, bleed, edema, infection Mind: emotions, memory Treatment: Dexamethasone 4-16 mg po/iv per day, divide 1-2 times/day Benzodiazepines for anticipatory nausea, anxietyinduced nausea, and refractory nausea Note: No evidence for BZD as sole agent for tx of nausea. Dietary changes for taste and smell

26 Mechanisms of Nausea and Vomiting Higher cortical structures Chemoreceptor trigger zone (4th ventricle) D2, 5HT3, NK1 Vestibular system Achm, H1 Vomiting Center: (Medulla) Achm, H1, 5HT2 N/V Mechanical stretch, GI irritation 5HT3 in GI tract, mechanoreceptors, vagal, splanchnic and glossopharyngeal nerves

27 Vestibular System Mediators: Histamine and Acetylcholine Associated with movement Etiology: Tumor, mets at base of skull Middle ear disease Stroke Treatment: Diphenhydramine Scopolamine patch 1.5mg q3d Promethazine Meclizine

28 Mechanism-Based Approach to Initial Management of N/V 1. Thorough evaluation to narrow DDx 2. Determine underlying pathway and neuroreceptor 3. Choose antiemetic targeted against neuroreceptor 4. Initiate antiemetic around-the-clock 5. Titrate antiemetic to max recommended dose if nausea persists 6. Add additional antiemetic aimed at different neurotransmitter if nausea persists 7. Evaluate for additional reversible mechanisms & treat

29 Intractable Nausea and Vomiting Combine antiemetics with different mechanisms of action Start with ATC dosing Add steroids (dexamethasone) Unclear mechanism of action Less impressive as single agents but quite effective in combination with other agents, such as Ondansetron Good for acute and delayed emesis

30 Intractable Nausea and Vomiting Nontraditional antiemetics: Mirtazapine 5HT3 antagonist mg po at bedtime. Can help w/ n/v, insomnia, appetite, mood Olanzapine D2, 5HT3, AchM Can help w/ n/v, delirium, anxiety, insomnia, and cachexia Consider bowel obstruction

31 Nausea and Vomiting Other Considerations Medications Route of administration Frequency of dosing, ATC vs PRN Anticipate nausea triggers and premedicate w/ antiemetic. Cost Food Small, frequent, attractive meals Consider odor, fat content Cool carbonated beverages Take medications, except antiemetics, after meals Acupuncture, Acupressure Imagery

32 Nausea and Vomiting Other Considerations Tetrahydrocannabinol (THC) The active ingredient of marijuana Marketed as dronabinol More effective than placebo in preventing chemotx-induced n/v Mediated by cannabinoid receptors at Vomiting Center in medulla Side effects: Drowsiness, orthostatic hypotension, tachycardia, dry mouth Anxiety, depression, visual hallucinations, and manic psychosis may occurs, especially in older individuals and patients who have never used marijuana.

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